title: Caspase inhibitor decreases apoptosis in pyrogallol-treated lung cancer Calu-6 cells via the prevention of GSH depletion.
abstract: Pyrogallol (PG) is a polyphenol compound and is known to be an O2.- generator. In the present study, we evaluated the anti-apoptotic effects of caspase inhibitors in relation to changes in reactive oxygen species (ROS) and glutathione (GSH) levels in PG-treated human pulmonary adenocarcinoma Calu-6 cells. Treatment with 50 microM PG inhibited the growth of Calu-6 cells approximately 60% and induced apoptosis approximately 17% at 24 h, accompanied by mitochondrial membrane potential loss (DeltaPsim). Treatment with pan-caspase inhibitor (Z-VAD-FMK), caspase-3 inhibitor (Z-DEVD-FMK), caspase-8 inhibitor (Z-IETD-FMK) and caspase-9 inhibitor (Z-LEHD-FMK) significantly prevented apoptosis in PG-treated Calu-6 cells at 24 h. PG increased the ROS and depleted GSH contents in Calu-6 cells. Treatment with each caspase inhibitor did not significantly change the ROS and GSH levels in PG-treated Calu-6 cells at 24 h. However, Z-VAD significantly prevented GSH depletion in PG-treated Calu-6 cells at the late time phase of 72 h. Conclusively, the anti-apoptotic effect of caspase inhibitor on PG-induced Calu-6 cell death was closely related to changes in GSH content rather than ROS levels.
authors.affiliation: Department of Physiology, Medical School, Institute for Medical Sciences, Centers for Healthcare Technology Development, Chonbuk National University, JeonJu 561-180, Korea.
authors.forename: Yong Hwan
authors.initials: YH
authors.lastname: Han
authors.forename: Suhn Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Sung Zoo
authors.initials: SZ
authors.lastname: Kim
authors.forename: Woo Hyun
authors.initials: WH
authors.lastname: Park
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011748:Pyrogallol / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
chemical_list: D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D017382:Reactive Oxygen Species; D011748:Pyrogallol; D020169:Caspases; D005978:Glutathione